Osteoarthritis of Multiple Joints of Ankle or FootPhase 4OPIOVASCNCT03781544
Effects of Opioids and NSAIDs on Sympathetic Nervous System and Vascular Function
A Phase 4 study testing Tramadol, Paracetamol and Diclofenac in people with Osteoarthritis of Multiple Joints of Ankle or Foot and Healthy, run by University of Zurich at 1 site in Switzerland.
Trial summary
Evaluation of the effect of different analgesic treatments (Tramadol, Paracetamol, Diclofenac) on sympathetic nerve activity, blood pressure, heart rate, heart rate, and vascular function in osteoarthritis patients and healthy subjects. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Osteoarthritis of Multiple Joints of Ankle or Foot, Healthy
- What is being tested?
- Tramadol, Paracetamol and Diclofenac
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Jan 2019to 31 Dec 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients ≥ 18 years of age, male or female, with a diagnosis of osteoarthritis or healthy subjects ≥ 18 years of age;
- Written informed consent;
Who cannot join
- History of hypersensitivity or allergy to any of the study drugs
- Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major CV surgery, percutaneous coronary intervention (PCI) or carotid angioplasty within the 3 months prior to Visit 1;
- Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 3 months after Visit 1;
- Presence of significant endocrine diseases;
- Presence of active acute infectious diseases;
- Known narrow-angle glaucoma;
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- Known epilepsy;
- Cimino-shunt operation on both arms;
- Pregnancy, intention thereof during study, lack of sufficient contraception, breastfeeding;
- Drug or alcohol abuse;
Trial locations and contacts
1 site in 1 country.
Switzerland1 site, 1 recruiting
- Recruiting
University Heart Center Zurich
Zurich, 8091
Frank Ruschitzka, MD, +41442553353, frank.ruschitzka@usz.ch
About this study
Official title: Effect of Opioids and NSAIDs on Sympathetic Nervous System and Vascular Function in Healthy Subjects and Patients With Osteoarthritis
Evaluation of the effect of different analgesic treatments (Tramadol, Paracetamol, Diclofenac) on sympathetic nerve activity, blood pressure, heart rate, heart rate, and vascular function in osteoarthritis patients and healthy subjects.
Read the detailed description
Hundreds of millions of patients worldwide require pain-relieving therapy to maintain an acceptable quality of life. Pain relievers, including non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, however, exert unwanted potent adverse systemic off-target effects and their use is associated with a well-documented excess of cerebrovascular and cardiovascular events. This of particular concern for the one fourth of the world's population aged over 35 years suffering from chronic pain, particularly with arthritis of whom half also present with established or at high risk of cardiovascular disease. This uncertainty around the cardiovascular safety of pain relieving drugs leaves practitioners and their patients with difficult management decisions and underscores the need to investigate potential differential cardiovascular effects of NSAIDs and opioids and to better delineate the underlying mechanisms involved. Indeed, currently available NSAIDs invariably disrupt the balance between prostacyclin and thromboxane, but may also exert multiple and opposing cardiovascular effects on endothelial factors, including nitric oxide and reactive oxygen species, the sympathetic nervous system and vascular inflammation. Intriguingly, the net effect of pain relieving drugs on vascular function and sympathetic nerve activity and its resulting deterioration of blood pressure control is increasingly recognized as a major possible determinant in explaining the cardiovascular side effects of NSAIDs. As a result of the ongoing concerns around the cardiovascular safety of NSAIDs and coxibs many patients are being withheld effective pain relieve or switched to opioids and/or paracetamol under the assumption of their yet unproven greater cardiovascular safety. The absence of evidence about the cardiovascular safety of these drugs presents a major dilemma for patients and physicians, who have been warned about the toxicity of NSAIDs.
- Being tested
- Tramadol, Paracetamol, Diclofenac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TramadolDrug
Also called Tramadol-Mepha
A single i.v. infusion of Tramadol (dose: 400mg/100ml) will be administered to the participants (treatment arm).
ParacetamolDrug
Also called PARACETAMOL Sintetica
A single i.v. infusion of Paracetamol (dose: 1g/100ml) will be administered to the participants (control arm).
DiclofenacDrug
A single i.v. infusion of Diclofenac (dose: 75mg/100ml) will be administered to the participants (treatment arm).
| Study group | Role | What they receive |
|---|---|---|
| Diclofenac | Experimental | Diclofenac (Diclofenacum natricum) A single i.v. infusion of Diclofenac (dose: 75mg/100ml) will be administered to the participants (treatment arm). Receives: Drug: Diclofenac |
| Paracetamol | Active comparator | Paracetamol (Paracetamol Sintetica):
A single i.v. infusion of Paracetamol (dose: 1g/100ml) will be administered to the participants (control arm). Receives: Drug: Paracetamol |
| Tramadol | Experimental | Tramadol (Tramadol-Mepha):
A single i.v. infusion of Tramadol (dose: 400mg/100ml) will be administered to the participants (treatment arm). Receives: Drug: Tramadol |
What is being measured
The primary outcome is the main question the study is designed to answer.
resting MSNA (sympathetic nervous activity )
Effect of different single analgesic treatments (Tramadol, Paracetamol, Diclofenac) on resting muscle sympathetic nerve activity (MSNA) in osteoarthritis patients (post 2 days of analgesic therapy washout phase) and in healthy subjects.
Tramadol treatment will be compared to diclofenac and paracetamol (3 treatment arms).
90 participants (45 osteoarthritis patients, 45 healthy subjects);
Single infusion of Tramadol (50 mg i.v.) Single infusion of Paracetamol (1000 mg i.v.) Single infusion of Diclofenac (75 mg i.v.)
Measured: 1day (110 min)
changes in FMD (Flow mediated vasodilation)
Effect of a single acute intravenous analgesic treatment with tramadol versus paracetamol on changes in flow mediated dilatation (FMD) in osteoarthritis patients and in healthy subjects.
Tramadol treatment will be compared with paracetamol as we previously demonstrated that paracetamol exerts no significant effects on endothelial function as measured by flow mediated dilatation.
80 participants (40 osteoarthritis patients, 40 healthy subjects);
Single infusion of Tramadol (50 mg i.v.) Single infusion of Paracetamol (1000 mg i.v.)
Measured: 1 day (210min)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2018
- Study start1 Jan 2019
- Primary completion31 Jul 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteoarthritis of Multiple Joints of Ankle or FootStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Frank Ruschitzka, MD, Study director, Cardiology, University Heart Center Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03781544
- Sponsor's protocol ID
- OPIOVASC
- Acronym
- OPIOVASC
- Status last verified
- May 2024
- First submitted
- 3 Dec 2018
- Last updated
- 17 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Opioids and NSAIDs on Sympathetic Nervous System and Vascular Function in Healthy Subjects and Patients With Osteoarthritis
- ClinicalTrials.gov ID
- NCT03781544
- Acronym / sponsor ID
- OPIOVASC / OPIOVASC
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 31 Jul 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 20 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Evaluation of the effect of different analgesic treatments (Tramadol, Paracetamol, Diclofenac) on sympathetic nerve activity, blood pressure, heart rate, heart rate, and vascular function in osteoarthritis patients and healthy subjects.
Detailed description
Hundreds of millions of patients worldwide require pain-relieving therapy to maintain an acceptable quality of life. Pain relievers, including non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, however, exert unwanted potent adverse systemic off-target effects and their use is associated with a well-documented excess of cerebrovascular and cardiovascular events. This of particular concern for the one fourth of the world's population aged over 35 years suffering from chronic pain, particularly with arthritis of whom half also present with established or at high risk of cardiovascular disease. This uncertainty around the cardiovascular safety of pain relieving drugs leaves practitioners and their patients with difficult management decisions and underscores the need to investigate potential differential cardiovascular effects of NSAIDs and opioids and to better delineate the underlying mechanisms involved. Indeed, currently available NSAIDs invariably disrupt the balance between prostacyclin and thromboxane, but may also exert multiple and opposing cardiovascular effects on endothelial factors, including nitric oxide and reactive oxygen species, the sympathetic nervous system and vascular inflammation. Intriguingly, the net effect of pain relieving drugs on vascular function and sympathetic nerve activity and its resulting deterioration of blood pressure control is increasingly recognized as a major possible determinant in explaining the cardiovascular side effects of NSAIDs. As a result of the ongoing concerns around the cardiovascular safety of NSAIDs and coxibs many patients are being withheld effective pain relieve or switched to opioids and/or paracetamol under the assumption of their yet unproven greater cardiovascular safety. The absence of evidence about the cardiovascular safety of these drugs presents a major dilemma for patients and physicians, who have been warned about the toxicity of NSAIDs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Diclofenac | Experimental | Drug: DiclofenacDiclofenac (Diclofenacum natricum) A single i.v. infusion of Diclofenac (dose: 75mg/100ml) will be administered to the participants (treatment arm). |
| Paracetamol | Active comparator | Drug: ParacetamolParacetamol (Paracetamol Sintetica): A single i.v. infusion of Paracetamol (dose: 1g/100ml) will be administered to the participants (control arm). |
| Tramadol | Experimental | Drug: TramadolTramadol (Tramadol-Mepha): A single i.v. infusion of Tramadol (dose: 400mg/100ml) will be administered to the participants (treatment arm). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients ≥ 18 years of age, male or female, with a diagnosis of osteoarthritis or healthy subjects ≥ 18 years of age;
- Written informed consent;
Key exclusion criteria (10 listed)
- History of hypersensitivity or allergy to any of the study drugs
- Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major CV surgery, percutaneous coronary intervention (PCI) or carotid angioplasty within the 3 months prior to Visit 1;
- Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 3 months after Visit 1;
- Presence of significant endocrine diseases;
- Presence of active acute infectious diseases;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TramadolAlso: Tramadol-MephaA single i.v. infusion of Tramadol (dose: 400mg/100ml) will be administered to the participants (treatment arm). | Drug | Tramadol |
| ParacetamolAlso: PARACETAMOL SinteticaA single i.v. infusion of Paracetamol (dose: 1g/100ml) will be administered to the participants (control arm). | Drug | Paracetamol |
| DiclofenacA single i.v. infusion of Diclofenac (dose: 75mg/100ml) will be administered to the participants (treatment arm). | Drug | Diclofenac |
Primary outcome
resting MSNA (sympathetic nervous activity )
Time frame: 1day (110 min)
Effect of different single analgesic treatments (Tramadol, Paracetamol, Diclofenac) on resting muscle sympathetic nerve activity (MSNA) in osteoarthritis patients (post 2 days of analgesic therapy washout phase) and in healthy subjects. Tramadol treatment will be compared to diclofenac and paracetamol (3 treatment arms). 90 participants (45 osteoarthritis patients, 45 healthy subjects); Single infusion of Tramadol (50 mg i.v.) Single infusion of Paracetamol (1000 mg i.v.) Single infusion of Diclofenac (75 mg i.v.)
changes in FMD (Flow mediated vasodilation)
Time frame: 1 day (210min)
Effect of a single acute intravenous analgesic treatment with tramadol versus paracetamol on changes in flow mediated dilatation (FMD) in osteoarthritis patients and in healthy subjects. Tramadol treatment will be compared with paracetamol as we previously demonstrated that paracetamol exerts no significant effects on endothelial function as measured by flow mediated dilatation. 80 participants (40 osteoarthritis patients, 40 healthy subjects); Single infusion of Tramadol (50 mg i.v.) Single infusion of Paracetamol (1000 mg i.v.)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2024.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank Ruschitzka, MD study director
Cardiology, University Heart Center Zurich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tramadol, Paracetamol and Diclofenac in people with Osteoarthritis of Multiple Joints of Ankle or Foot and Healthy, run by University of Zurich at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Isabella Sudano, MD (+41442555841, Isabella.Sudano@usz.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
resting MSNA (sympathetic nervous activity ) (time frame: 1day (110 min)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2024; AzTrials last refreshed its copy on 8 Nov 2026.